Using the TI.VA algorithm to titrate the depth of general anaesthesia: a first-in-humans study

Abstract

Background: The dose of anaesthetic and opioid drugs must be continuously adjusted after the induction of general anaesthesia to maintain an adequate depth of anaesthesia. The TI.VA algorithm is a multiple-input/multiple-output algorithm designed to optimise the balance between anaesthetic and opioid concentrations during general anaesthesia. It applies vector analysis to a two-dimensional matrix to quantify any inadequacy of the depth of anaesthesia at any given moment and determine any drug dose adjustments required to achieve an adequate depth of anaesthesia. This study aimed to capture preliminary data on the performance and safety of the TI.VA algorithm during total i.v. anaesthesia in patients.

Methods: This prospective study enrolled nine patients with breast cancer scheduled to undergo surgery. General anaesthesia was induced under manual control using propofol and remifentanil. Anaesthesia was guided using the TI.VA algorithm from skin incision until surgical resection was completed. The quality of anaesthesia was assessed through an analysis of performance errors. A bispectral index global score (GS_BIS) <50 was considered an acceptable target for algorithm performance.

Results: All nine procedures were completed without any adverse events and none of the patients recalled any intraoperative event. Overall, we analysed 3417 monitoring points corresponding to 285 min of surgery. All patients presented a GS_BIS below the cut-off value of 50.

Conclusions: The TI.VA algorithm provides adequate control of clinical anaesthesia. A more sophisticated prototype needs to be developed before the trial is expanded to include larger patient populations.

Clinical trial registration: NCT05199883.

Keywords: computer-assisted decision-making; intravenous anaesthesia; medication systems; pharmacology.

Fig 1

TI.VA prototype. The components of the first prototype system for managing the TI.VA algorithm are shown. The MacBook® screen shows the user interface constructed using a number spreadsheet (Apple Inc., Cupertino, CA, USA). The same stand holds the BIS™ monitor (Medtronic, Dublin, Ireland) and the Alaris® Gateway Workstation (Becton-Dickinson, Co., Franklin Lakes, NJ, USA), with two target-controlled infusion pumps dedicated to propofol and remifentanil administration. Communication of the Alaris® workstation with the MacBook is enabled using an Ethernet port, while communication with the bispectral index system is achieved using an RS232 port. The CNAP® monitor (CNSystems Medizintechnik GmbH, Graz, Austria) is connected via a separate port. In this case, the implementation of a communication interface with numbers is more problematic. Thus, we ultimately decided on optical character recognition technology guaranteed by a camera mounted in front of the monitor. The monitor screen is masked to optimise the recognition process. Data (i.e. mean arterial pressure and heart rate) are shown in the window directly in front of the camera. TI.VA, total intravenous anaesthesia.

Fig 2

Anaesthetic drug concentrations during TI.VA control of anaesthesia. Concentrations are expressed as target effect-site levels. TI.VA, total intravenous anaesthesia.